A living organism has control mechanisms for maintaining various electrolytes in body fluid at their optimum levels, in order to control its body water content. Hormones known to control electrolyte and water metabolisms include aldosterone (mineral corticoid secreted from the adrenal cortex) and vasopressin (posterior pituitary hormone). There are also various diseases known to result from abnormalities of these hormones. Examples of such diseases resulting from hormone abnormalities include hyposupradrenalism (Addison's disease), hyperaldosteronism, posterior pituitary gland hypergasia (diabetes insipidus), and vasopressin secretion abnormality.
On the other hand, the clinical pathology of HHM (humoral hypercalcemia of malignancy) shows a variety of clinical symptoms as presented below (Kanji SATO, “Hypercalcemia Q & A,” published by Iyaku Journal Co., Ltd., Japan):
constitutional symptoms including lassitude, systemic malaise, loss of appetite, loss of weight, mouth dryness, and anemia;
digestive symptoms including constipation, peptic ulcer, and acute pancreatitis;
kidney functions including polyposia, polyuria, mouth dryness, and andurinary calculus;
neuromuscular symptoms including weakness, and loss of muscle strength;
psychoneurotic symptoms including retention disorder, loss of thinking ability, clouding of consciousness, and coma; and
respiratory symptoms including hypoxemia, and polypnea.
Among these symptoms, polyposia, polyuria, mouth dryness and the like are particularly characteristic clinical symptoms of hypercalcemia.
Parathyroid hormone-related peptide (PTHrP) is known to cause HHM. The mechanism of developing HHM attributable to PTHrP produced by malignant tumors involves the promotion of both bone resorption and calcium reabsorption from the kidneys. Once hypercalcemia is developed, it is known that polyuria, anorexia, nausea or vomiting results in dehydration and an increased blood concentration, thereby leading to further progress of hypercalcemia.